AD GWAS Summary Statistics#

Summary statistics from large-scale Alzheimer’s disease GWAS used as primary trait input for fine-mapping, TWAS, and colocalization analyses in the FunGen-xQTL flagship study.

All summary statistics were harmonized to GRCh38 prior to downstream analyses. The APOE region (chr19:44.4–46.5 Mb) was handled separately due to its complex LD structure. A custom LD reference panel was constructed from 16,905 ADSP whole-genome sequenced samples of European ancestry.

Datasets#

Six datasets from four AD meta-analyses were used, encompassing clinically confirmed late-onset AD, proxy-based AD cases, and broader dementia phenotypes.

Study	Population	N cases	N controls	Phenotype definition	Notes
Bellenguez et al. 2022 Nat Genet	European	111,326	677,663	Clinically confirmed late-onset AD	Primary GWAS; used throughout
Wightman et al. 2021 Nat Genet	European	90,338	1,036,225	AD + proxy-AD (UK Biobank)	Proxy-based phenotype included
Kunkle et al. 2019 Nat Genet	European	21,982	41,944	Clinically confirmed late-onset AD	ADGC/IGAP
Jansen et al. 2019 Nat Genet	European	—	—	AD + proxy-AD (UK Biobank)	Meta-analysis with IGAP
Lambert et al. 2013 Nat Genet	European	17,008	37,154	Clinically confirmed late-onset AD	IGAP stage 1; historical reference
Broader dementia phenotype	European	—	—	Broader dementia definition	Fourth meta-analysis source

Quality Control#

Summary statistics were processed through a QC pipeline built around SLALOM, supplemented by manual curation comparing single-effect regression and conditional regression outputs to exclude suspicious or unstable loci. After QC, 170 AD-associated loci were retained for fine-mapping.

LD Reference Panel#

Panel	N samples	Population	Build	Synapse ID
ADSP WGS	16,905	European ancestry	GRCh38	syn69670651 → `EUR/` (syn69670652)

Data Access#

Resource	Description	Synapse ID
ADSP LD reference (EUR)	Custom LD panel for fine-mapping and colocalization	syn69670652
LDSC reference data	LD scores, munged GWAS, sLDSC annotations	syn69670653
LDSC munged GWAS	Pre-munged AD GWAS summary statistics	syn69670656
AD GWAS fine-mapping models	Fine-mapping outputs per GWAS dataset	syn69670625
AD fine-mapping results	Fine-mapped loci and credible sets	syn69696846
Top loci unified summary	`AD_GWAS_finemapping_109_blocks_top_loci_unified_any0.8ANDmin0.5.csv.gz`	syn69865824

All resources are in the FunGen-xQTL staging folder: syn68872650 (staging)

Abbreviations#

Abbreviation	Full name
AD	Alzheimer’s disease
GWAS	Genome-wide association study
ADSP	Alzheimer’s Disease Sequencing Project
IGAP	International Genomics of Alzheimer’s Project
ADGC	Alzheimer’s Disease Genetics Consortium
LD	Linkage disequilibrium
WGS	Whole-genome sequencing
QC	Quality control
sLDSC	Stratified linkage disequilibrium score regression